LAUSR

Dear Editor, Lineage switch between myeloid and lymphoblastic leukemia is a rare but interesting event as its exploration might give insights into pathways responsible for lineage assignment and development of leukemia. Lineage switch describes an acute leukemia that meets French-American-British (FAB) criteria for one lineage but converts to the opposite lineage upon relapse. Lineage switches are associated with poor prognosis and resistance to therapy [1, 2]. Here, we describe a linage switch from a T-cell acute lymphoblastic leukemia (T-ALL) to a myeloid sarcoma in a patient who was cured by second allogeneic stem cell transplantation (SCT). The 32-year-old male patient was first diagnosed with a cortical T-ALL. He had been treated with polychemotherapy according to the German Multicenter Study Group (GMALL) 07/2003 protocol, during which a relapse had occurred. After salvage chemotherapy with cladribine, etoposide, and cytarabine, he had achieved a second complete remission (CR) and a first allogeneic SCTwas performed (conditioning: cyclophosphamide/12 Gy TBI). The patient presented 7 years later with a mediastinal tumor and lymphadenopathy. A biopsy obtained from the mediastinal tumor revealed a blast cell infiltrate positive for CD34, CD10, and CD45. In contrast to the previous T-ALL (Fig. 1a–c), the infiltrate showed positivity for the myeloid antigens CD33 and intracellular myeloperoxidase and negativity for T cell antigens (Fig. 1e–g). The clonal relation of the myeloid sarcoma to the initial disease was proven by detection of the same biallelic clonal T cell receptor gamma-chain rearrangements (Fig. 1d, h). Chimerism analyses of blood and bone marrow showed a complete donor cell chimerism. Despite intensive salvage therapies with cytarabine/daunorubicin, cytarabine/mitoxantrone, and nelarabine/ifosfamide, no remission could be achieved, and a second allogeneic SCT from a different donor (conditioning: fludarabine, busulfane, cyclophosphamide) followed by a consolidating mediastinal radiotherapy was performed. These therapies led to an ongoing CR confirmed by PET-CT. Actually, after 2 years, the patient is well in a sustained CR. Reasons for lineage switches remain unclear. Either an emergence of a minor subclone which had already been present at initial diagnosis or a phenotypic shift of the original clone are the two main explanations. Mutations in early hematopoietic progenitor cells before lineage differentiation, e.g., of the DNMT3A gene, can lead to a preleukemic state [3]. However, due to poor sample quality, we were not able to detect any mutations. So far, there are only two more cases described in literature in which the clonal relation of a lineage switch from T-lymphoblastic to myeloid lineage was proven by analysis of molecular markers [4, 5], while in several other cases, the clonal relation was proven by conventional cytogenetic analyses [6–8]. In our patient, the disease was refractory to chemotherapy and only responded to a second allogeneic SCT, suggesting that allogeneic SCT may represent a * Matthias Stelljes [email protected]